EP3893891A1 - Formes solides d'un inhibiteur de cd73 et leur utilisation - Google Patents

Formes solides d'un inhibiteur de cd73 et leur utilisation

Info

Publication number
EP3893891A1
EP3893891A1 EP19896971.9A EP19896971A EP3893891A1 EP 3893891 A1 EP3893891 A1 EP 3893891A1 EP 19896971 A EP19896971 A EP 19896971A EP 3893891 A1 EP3893891 A1 EP 3893891A1
Authority
EP
European Patent Office
Prior art keywords
compound
solid form
degrees
xrpd
cancer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP19896971.9A
Other languages
German (de)
English (en)
Other versions
EP3893891A4 (fr
Inventor
Jenna Leigh JEFFREY
Kenneth V. LAWSON
Dillon Harding MILES
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Arcus Biosciences Inc
Original Assignee
Arcus Biosciences Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Arcus Biosciences Inc filed Critical Arcus Biosciences Inc
Publication of EP3893891A1 publication Critical patent/EP3893891A1/fr
Publication of EP3893891A4 publication Critical patent/EP3893891A4/fr
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/28—Compounds containing heavy metals
    • A61K31/282—Platinum compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/243—Platinum; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/23—Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22

Definitions

  • the present invention relates to solid forms of a compound that modulates the conversion of AMP to adenosine by 5'-nucleotidase, ecto (NT5E or 5NT; also known as CD73), and compositions (e.g., pharmaceutical compositions) comprising the compound.
  • a compound in a solid form
  • methods of preparation, methods of use, and compositions are described in detail below.
  • cancers that can be treated using the solid form of a compound of Formula (I) and compositions described herein include, but are not limited to: cancers of the prostate, colorectum, pancreas, cervix, stomach, endometrium, brain, liver, bladder, ovary, testis, head, neck, skin (including melanoma and basal carcinoma), mesothelial lining, white blood cell (including lymphoma and leukemia) esophagus, breast, muscle, connective tissue, lung
  • the present invention contemplates methods for treating or preventing an infective disorder (e.g., a viral infection) in a subject (e.g., a human) comprising administering to the subject a therapeutically effective amount of a solid form of a compound of Formula (I).
  • an infective disorder e.g., a viral infection
  • the infective disorder is a viral infection (e.g., a chronic viral infection), a bacterial infection, a fiingal infection, or a parasitic infection.
  • the viral infection is human immunodeficiency vims or cytomegalovirus.
  • administration refers to contact of, for example, an inhibitor of CD73, a pharmaceutical composition comprising same, or a diagnostic agent to the subject, cell, tissue, organ, or biological fluid.
  • administration includes contact (e.g., in vitro or ex vivo) of a reagent to the cell, as well as contact of a reagent to a fluid, where the fluid is in contact with the cell.
  • the terms“treat”,“treating”, treatment” and the like refer to a course of action (such as administering an inhibitor of CD73 or a pharmaceutical composition comprising same) initiated after a disease, disorder or condition, or a symptom thereof, has been diagnosed, observed, and the like so as to eliminate, reduce, suppress, mitigate, or ameliorate, either temporarily or permanently, at least one of the underlying causes of a disease, disorder, or condition afflicting a subject, or at least one of the symptoms associated with a disease, disorder, condition afflicting a subject.
  • treatment includes inhibiting (e.g., arresting the development or further development of the disease, disorder or condition or clinical symptoms association therewith) an active disease.
  • inhibitors and“antagonists”, or“activators” and“agonists” refer to inhibitory or activating molecules, respectively, for example, for the activation of, e.g., a ligand, receptor, cofactor, gene, cell, tissue, or organ.
  • Inhibitors are molecules that decrease, block, prevent, delay activation, inactivate, desensitize, or down-regulate, e.g., a gene, protein, ligand, receptor, or cell.
  • Activators are molecules that increase, activate, facilitate, enhance activation, sensitize, or up-regulate, e.g., a gene, protein, ligand, receptor, or cell.
  • ligand/receptor, antibody/antigen, or other binding pair indicates a binding reaction which is determinative of the presence of the protein in a heterogeneous population of proteins and other biologies.
  • a specified ligand binds to a particular receptor and does not bind in a significant amount to other proteins present in the sample.
  • the antibody, or binding composition derived from the antigen-binding site of an antibody, of the contemplated method binds to its antigen, or a variant or mutein thereof, with an affinity that is at least two fold greater, at least ten times greater, at least 20-times greater, or at least 100-times greater than the affinity with any other antibody, or binding composition derived therefrom.
  • variants and homologs encompass naturally occurring DNA sequences and proteins encoded thereby and their isoforms, as well as splice variants of a protein or gene.
  • the terms also encompass nucleic acid sequences that vary in one or more bases from a naturally-occurring DNA sequence but still translate into an amino acid sequence that corresponds to the naturally-occurring protein due to degeneracy of the genetic code.
  • Non-naturally-occurring variants and homologs include polypeptides and nucleic acids that comprise a change in amino acid or nucleotide sequence, respectively, where the change in sequence is artificially introduced (e.g., muteins); for example, the change is generated in the laboratory by human intervention (“hand of man”). Therefore, non-naturally occurring variants and homologs may also refer to those that differ from the naturally-occurring sequences by one or more conservative substitutions and/or tags and/or conjugates.
  • cDNA complementary DNA
  • vectors vectors, probes, primers and the like.
  • the present invention provides solid forms of (((((2R,3S,4R,5R)-5-(6-chloro-4-(((S)-l- (2-fluorophenyl)ethyl)amino)- 1 H-pyrazolo[3 ,4-b]pyridin- 1 -yl)-3 ,4-dihydroxytetrahydrofuran-2- yl)methoxy)(hydroxy)phosphoryl)methyl)phosphonic acid: (Compound I), including crystalline and amorphous forms, as well as solvate and hydrate forms. [0068] In some embodiments, the present invention provides a solid form, e.g., a crystalline form, of Compound I having the structure:
  • solid Form A of Compound I can be characterized by an X-ray powder diffraction pattern (XRPD) having peaks at 6.1, 6.4, 10.1 , 11.7, 16, 16.6, 18.1 , 19.4, 21, 21.4, 21.9, 22.4, 24.4, 25.6, 27.3, 28.3, and 29.4 degrees 20 ( ⁇ 0.1 degrees 20), wherein the XRPD is made using CuK ai radiation, or a differential scanning calorimetry (DSC) plot characterized by a DSC endotherm at about 168 °C followed by a exotherm at about 188 °C.
  • XRPD X-ray powder diffraction pattern
  • the solid Form A of Compound I can be characterized by an X-ray powder diffraction pattern having five or more peaks at 6.1, 6.4, 10.1, 1 1.7, 16, 16.6, 18.1, 19.4, 21 , 21.4, 21.9, 22.4, 24.4, 25.6, 27.3, 28.3, or 29.4 degrees 20 ( ⁇ 0.1 degrees 20), wherein the XRPD is made using CuK ai radiation.
  • the solid Form A of Compound I can be characterized by an X-ray powder diffraction pattern having five or more peaks at 6.1, 6.4, 10.1, 1 1.7, 16, 16.6, 18.1, 19.4, 21 , 21.4, 21.9, 22.4, 24.4, 25.6, 27.3, 28.3, or 29.4 degrees 20 ( ⁇ 0.1 degrees 20), wherein the XRPD is made using CuK ai radiation.
  • the solid Form A of Compound I can be characterized by an X- ray powder diffraction pattern having six or more peaks at 6.1, 6.4, 10.1, 1 1.7, 16, 16.6, 18.1, 19.4, 21 , 21.4, 21.9, 22.4, 24.4, 25.6, 27.3, 28.3, or 29.4 degrees 20 ( ⁇ 0.1 degrees 20), wherein the XRPD is made using CuK ai radiation.
  • the solid Form A of Compound I can be characterized by an X- ray powder diffraction (XRPD) pattern having peaks at 6.1 , 6.4, 16.0, and 19.4 degrees 20 ( ⁇ 0.1 degrees 20), wherein the XRPD is made using CuK ai radiation.
  • the solid Form A of Compound I can be characterized by an X-ray powder diffraction (XRPD) pattern having peaks at 6.1, 6.4, 16.0, 19.4, 21.4 and 24.4 degrees 20 ( ⁇ 0.1 degrees 20), wherein the XRPD is made using CuK ai radiation.
  • the solid Form A of Compound I can be characterized by an X-ray powder diffraction (XRPD) pattern having peaks at 6.1 , 6.4, 16.0, 19.4, 21.4, 22.4 and 24.4 degrees 20 ( ⁇ 0.1 degrees 20), wherein the XRPD is made using
  • XRPD X-ray powder diffraction
  • the solid Form B of Compound I can be characterized by an X- ray powder diffraction pattern having six or more peaks at 5.5, 6.6, 10.4, 1 1.0, 12.9, 15.2, 16.5, 17.2, 17.7, 19.7, 20.3, 21.2, 22.7, 24.0, 25.3, 25.6, 28.2 and 30.3 degrees 20 ( ⁇ 0.1 degrees 20), wherein the XRPD is made using CuK ai radiation.
  • the solid Form B of Compound I can be characterized by an XRPD pattern having peaks at 5.5, 6.6 and 22.7 degrees 20 ( ⁇ 0.1 degrees 20), wherein the XRPD is made using CuK ai radiation.
  • the solid Form B of Compound I can be characterized by an X-ray powder diffraction (XRPD) pattern further comprising one or more peaks at 10.4, 11, 19.7 or 21.2 degrees 20 ( ⁇ 0.1 degrees 20), wherein the XRPD is made using CuK ai radiation.
  • XRPD X-ray powder diffraction
  • a competitive CD73 inhibitor is a compound that reversibly inhibits CD73 enzyme activity at the catalytic site;“a noncompetitive CD73 inhibitor” is a compound that reversibly inhibits CD73 enzyme activity at a non-catalytic site; and“an irreversible CD73 inhibitor” is a compound that irreversibly eliminates CD73 enzyme activity by forming a covalent bond (or other stable means of inhibiting enzyme function) with the enzyme.
  • CD73 inhibitors can modulate purinergic signaling, a type of extracellular signaling mediated by purine nucleotides and nucleosides such as ATP and adenosine.
  • Purinergic signaling involves the activation of purinergic receptors in the cell and/or in nearby cells, resulting in the regulation of cellular functions.
  • the enzymatic activity of CD73 plays a strategic role in calibrating the duration, magnitude, and chemical nature of purinergic signals delivered to various cells (e.g., immune cells).
  • CD73 inhibitors can be used to control tumor progression and metastasis. Other potential utilities are discussed elsewhere herein.
  • Modifications known in the art include pegylation, Fc-fusion and albumin fusion.
  • inflammatory disease “inflammatory condition”,“inflammatory disorder” and the like are meant to broadly encompass any immune-related condition (e.g., an autoimmune disease) or a disorder with an inflammatory component that can be treated by the solid form of a compound of Formula (I) described herein such that some therapeutic benefit is obtained. Such conditions frequently are inextricably intertwined with other diseases, disorders and conditions.
  • an“immune condition” may refer to proliferative conditions, such as cancer, tumors, and angiogenesis; including infections (acute and chronic), tumors, and cancers that resist eradication by the immune system.
  • the solid form of a compound of Formula (I) can be used to increase or enhance an immune response; to improve immunization, including increasing vaccine efficacy; and to increase inflammation. Immune deficiencies associated with immune deficiency diseases, immunosuppressive medical treatment, acute and/or chronic infection, and aging can be treated using the compounds disclosed herein.
  • the solid form of a compound of Formula (I) can also be used to stimulate the immune system of patients suffering from iatrogenically-induced immune suppression, including those who have undergone bone marrow transplants, chemotherapy, or radiotherapy.
  • the solid form of a compound of Formula (I) is used to increase or enhance an immune response to an antigen by providing adjuvant activity.
  • Tablets, capsules and the like contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients which are suitable for the manufacture of tablets.
  • excipients may be, for example, diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, com starch, or alginic acid; binding agents, for example starch, gelatin or acacia, and lubricating agents, for example magnesium stearate, stearic acid or talc.
  • Oily suspensions may be formulated by suspending the active ingredient in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin.
  • the oily suspensions may contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol. Sweetening agents such as those set forth above, and flavoring agents may be added to provide a palatable oral preparation.
  • the pharmaceutical compositions may be in the form of a sterile injectable aqueous or oleagenous suspension.
  • This suspension may be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents mentioned herein.
  • the sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example, as a solution in 1 ,3-butane diol.
  • such combination therapy may have a synergistic therapeutic or prophylactic effect on the underlying disease, disorder, or condition.
  • the solid form of the compound of Formula (I) may be used in combination with at least one other (active) agent in any manner appropriate under the circumstances.
  • treatment with the at least one active agent and the solid form of the compound of Formula (I) is maintained over a period of time.
  • treatment with the at least one active agent is reduced or discontinued (e.g., when the subject is stable), while treatment with the solid form of the compound of Formula (I) is maintained at a constant dosing regimen.
  • treatment with the at least one active agent is reduced or discontinued (e.g., when the subject is stable), while treatment with the solid form of the compound of Formula (I) is reduced (e.g., lower dose, less frequent dosing or shorter treatment regimen).
  • methotrexate platinum and platinum coordination complexes such as cisplatin and carboplatin; vinblastine; etoposide (VP- 16); ifosfamide; mitomycin C; mitoxantrone; vincristine; vinorelbine; navelbine; novantrone; teniposide; daunomycin; aminopterin; xeloda; ibandronate; CPT1 1;
  • immune checkpoints ligands and receptors
  • PD1 programmed cell death protein 1
  • PDL1 PD1 ligand
  • BTLA B and T lymphocyte attenuator
  • CTLA4 cytotoxic T-lymphocyte associated antigen 4
  • TIGIT T cell
  • TIM3 T-cell membrane protein 3
  • LAG3 lymphocyte activation gene 3
  • A2aR adenosine A2a receptor A2aR
  • Killer Inhibitory Receptors which can be divided into two classes based on their structural features: i) killer cell immunoglobulin-like receptors (KIRs), and ii) C-type lectin receptors (members of the type II transmembrane receptor family).
  • the present invention contemplates the use of the solid form of the compound of Formula (I) described herein in combination with inhibitors of the aforementioned immune- checkpoint receptors and ligands, as well as yet-to-be-described immune-checkpoint receptors and ligands.
  • Certain modulators of immune checkpoints are currently available, whereas others are in late-stage development.
  • the fully humanized CTLA4 monoclonal antibody ipilimumab (YERVOY; Bristol-Myers Squibb) became the first immune checkpoint inhibitor to receive regulatory approval in the US.
  • Approved anti-PDLl antibodies include avelumab (BAVENCIO, EMD Serono & Pfizer), atezolizumab (TECENTRIQ;
  • Examples of therapeutic agents useful in combination therapy are specific to the underlying disease, disorder or condition, and are known to the skilled artisan.
  • Microbial Diseases The present invention provides methods for treating and/or preventing viral, bacterial, fungal and parasitic diseases, disorders and conditions, as well as disorders associated therewith, with a solid form of the compound of Formula (I) and at least one additional therapeutic or diagnostic agent (e.g., one or more other antiviral agents and/or one or more agents not associated with viral therapy).
  • Embodiments of the present invention contemplate the use of the solid form of the compound of Formula (I) described herein in combination with agents useful in the treatment or prevention of bacterial disorders.
  • Antibacterial agents can be classified in various manners, including based on mechanism of action, based on chemical structure, and based on spectrum of activity. Examples of antibacterial agents include those that target the bacterial cell wall (e.g., cephalosporins and penicillins) or the cell membrane (e.g., polymyxins), or interfere with essential bacterial enzymes (e.g., sulfonamides, rifamycins, and quinolines).
  • Embodiments of the present invention contemplate the use of the solid form of the compound of Formula (I) described herein in combination with agents useful in the treatment or prevention of fungal disorders.
  • Antifungal agents include polyenes (e.g., amphotericin, nystatin, and pimaricin); azoles (e.g., fluconazole, itraconazole, and ketoconazole); allylamines (e.g., naftifine, and terbinafine) and morpholines (e.g., amorolfine); and antimetabolies (e.g., 5- fluorocytosine).
  • polyenes e.g., amphotericin, nystatin, and pimaricin
  • azoles e.g., fluconazole, itraconazole, and ketoconazole
  • allylamines e.g., naftifine, and terbinafine
  • morpholines e
  • TIL tumor-infiltrating lymphocytes
  • CAR chimeric antigen receptors
  • TCR T cell receptors
  • Adoptive cell therapy generally involves collecting T cells from an individual, genetically modifying them to target a specific antigen or to enhance their anti-tumor effects, amplifying them to a sufficient number, and infusion of the genetically modified T cells into a cancer patient.
  • T cells can be collected from the patient to whom the expanded cells are later reinfused (e.g., autologous) or can be collected from donor patients (e.g., allogeneic).
  • An effective dose is the dose or amount of an agent that produces a therapeutic response or desired effect in some fraction of the subjects taking it.
  • The“median effective dose” or ED50 of an agent is the dose or amount of an agent that produces a therapeutic response or desired effect in 50% of the population to which it is administered.
  • the ED50 is commonly used as a measure of reasonable expectance of an agent’s effect, it is not necessarily the dose that a clinician might deem appropriate taking into consideration all relevant factors.
  • the effective amount is more than the calculated ED50, in other situations the effective amount is less than the calculated ED50, and in still other situations the effective amount is the same as the calculated ED50.
  • kits may contain a label or packaging insert including identifying information for the components therein and instructions for their use (e.g., dosing parameters, clinical pharmacology of the active ingredient(s), including mechanism of action, pharmacokinetics and
  • Suitable solvents include but are not limited to acetone, tetrahydrofuran, ethanol, methanol, acetonitrile, and water.
  • the formation of the crystalline form can be sensitive to the ratio of solvent to precipitating solvent.
  • the ethanol to acetonitrile ratio can vary from 1 : 1 to 1 : 4.
  • the main effect is percent recovery of the crystalline form relative to the starting material.
  • acetonitrile With higher proportions of acetonitrile, a biphasic liquid will form, followed by crystallization of the denser phase.
  • a mixture of solvents is required and the ratio of solvents can vary from 4: 1 to 1 : 1.
  • the ratio or concentration of compound relative to solvent can be variable depending on the solvent or solvent mixture used. Typical concentrations can range from 150 mg/mL to 10 mg/mL with the limiting factor at the higher end being the solubility of the material or the ease of recovery the material once crystallization has occurred. For example, approximately 150 mg of amorphous material can be dissolved in 1 mL of ethanol with subsequent addition of acetonitrile added to afford the crystalline form.
  • Step 1 The heterocycle (25 g, 133 mmol) and ammonium sulfate (175 mg, 1 mol%) were charged in a 1 L round bottom flask equipped with a magnetic stir bar. HMDS (133 mL, 1M) was added and the mixture was refluxed for 4 hours under an air atmosphere (heating block temperature 155°C). Excess HMDS was evaporated under vacuum at 60°C and then the flask was placed under high vacuum at 45 °C for 30 minutes. This operation was repeated to make sure all excess HMDS was removed.
  • This change in water capacity is associated a phase change, as XRPD of the sample post- DVS shows loss of crystallinity and regeneration of amorphous material.
  • XRPD of the sample post- DVS shows loss of crystallinity and regeneration of amorphous material.
  • the material shows an increase of 13.2% wt. water relative to 0% relative humidity, indicating the material is hygroscopic.
  • the amount of water in the sample at 90% relative humidity corresponds to the pentahydrate of the material.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Inorganic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des formes solides du composé I, qui module la conversion de l'AMP en adénosine par l'ecto-5'-nucléotidase, ainsi que des compositions contenant ce composé et des procédés de préparation des formes solides. L'invention concerne également l'utilisation de la forme solide du composé I et des compositions dans le traitement et/ou la prévention d'un ensemble varié de maladies, troubles et affections, y compris de troubles liés au cancer et à l'immunité, qui sont médiés par l'ecto-5'-nucléotidase.
EP19896971.9A 2018-12-13 2019-12-12 Formes solides d'un inhibiteur de cd73 et leur utilisation Pending EP3893891A4 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862779064P 2018-12-13 2018-12-13
PCT/US2019/065916 WO2020123772A1 (fr) 2018-12-13 2019-12-12 Formes solides d'un inhibiteur de cd73 et leur utilisation

Publications (2)

Publication Number Publication Date
EP3893891A1 true EP3893891A1 (fr) 2021-10-20
EP3893891A4 EP3893891A4 (fr) 2022-08-03

Family

ID=71076117

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19896971.9A Pending EP3893891A4 (fr) 2018-12-13 2019-12-12 Formes solides d'un inhibiteur de cd73 et leur utilisation

Country Status (4)

Country Link
US (1) US11819512B2 (fr)
EP (1) EP3893891A4 (fr)
TW (1) TW202039527A (fr)
WO (1) WO2020123772A1 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2017206061B2 (en) 2016-01-08 2022-12-15 Arcus Biosciences, Inc. Modulators of 5'-nucleotidase, ecto and the use thereof
EP3761993A4 (fr) * 2018-03-09 2022-03-09 Arcus Biosciences, Inc. Médicaments renforçant l'immunité administrés par voie parentérale
US11819512B2 (en) 2018-12-13 2023-11-21 Arcus Biosciences, Inc. Solid forms of a CD73 inhibitor and the use thereof
US11633416B1 (en) 2020-03-06 2023-04-25 Arcus Biosciences, Inc. Oral formulations of CD73 compounds
EP4168120A1 (fr) 2020-06-17 2023-04-26 Arcus Biosciences, Inc. Formes cristallines d'un inhibiteur de cd73 et utilisations associées
WO2024086718A1 (fr) 2022-10-20 2024-04-25 Arcus Biosciences, Inc. Formulations lyophilisées de composés cd73

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9090697B2 (en) 2013-03-15 2015-07-28 Bayer Healthcare Llc Methods for treating bleeding disorders
EP3134411B1 (fr) 2014-04-25 2021-06-30 Boehringer Ingelheim International GmbH Dérivés de la purine en tant qu'inhibiteurs pour le traitement du cancer
AU2017206061B2 (en) 2016-01-08 2022-12-15 Arcus Biosciences, Inc. Modulators of 5'-nucleotidase, ecto and the use thereof
EP3761993A4 (fr) 2018-03-09 2022-03-09 Arcus Biosciences, Inc. Médicaments renforçant l'immunité administrés par voie parentérale
US11819512B2 (en) 2018-12-13 2023-11-21 Arcus Biosciences, Inc. Solid forms of a CD73 inhibitor and the use thereof
EP4168120A1 (fr) 2020-06-17 2023-04-26 Arcus Biosciences, Inc. Formes cristallines d'un inhibiteur de cd73 et utilisations associées

Also Published As

Publication number Publication date
US20220062313A1 (en) 2022-03-03
WO2020123772A1 (fr) 2020-06-18
US11819512B2 (en) 2023-11-21
EP3893891A4 (fr) 2022-08-03
TW202039527A (zh) 2020-11-01

Similar Documents

Publication Publication Date Title
US11667662B2 (en) Modulators of 5′-nucleotidase, ecto and the use thereof
US11267845B2 (en) Inhibitors of CD73-mediated immunosuppression
US11819512B2 (en) Solid forms of a CD73 inhibitor and the use thereof
CN110049767B (zh) 腺苷5′-核苷酸酶的抑制剂
EP3634417B1 (fr) Dérivés quinazoline-pyrazole pour le traitement de troubles liés au cancer
US20200405629A1 (en) Parenterally administered immune enhancing drugs
US20220016143A1 (en) Inhibitors of arg1 and/or arg2
US11649261B2 (en) Crystalline forms of a CD73 inhibitor and uses thereof

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20210708

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 40062382

Country of ref document: HK

A4 Supplementary search report drawn up and despatched

Effective date: 20220704

RIC1 Information provided on ipc code assigned before grant

Ipc: A61P 35/00 20060101ALI20220628BHEP

Ipc: A61K 31/7076 20060101ALI20220628BHEP

Ipc: A61K 31/7064 20060101ALI20220628BHEP

Ipc: C07H 19/23 20060101AFI20220628BHEP